Yttria and Ceria Doped Zirconia Thin Films Grown by Pulsed Laser Deposition

The Yttria stabilized Zirconia (YSZ) is a standard electrolyte for solid oxide fuel cells (SOFCs), which are potential candidates for next generation portable and mobile power sources. YSZ electrolyte thin films having a cubic single phase allow reducing the SOFC operating temperature without diminishing the electrochemical power density. Films of 8 mol % Yttria stabilized Zirconia (8YSZ) and films with addition of 4 weight % Ceria (8YSZ + 4CeO2) were grown by pulsed laser deposition (PLD) technique using 8YSZ and 8YSZ + 4CeO2 targets and a Nd-YAG laser (355 nm). Films have been deposited on Soda-Calcia-Silica glass and Si(100) substrates at room temperature. The morphology and structural characteristics of the samples have been studied by means of X-ray diffraction and scanning electron microscopy. Films of a cubic-YSZ single phase with thickness in the range of 1-3 µm were grown on different substrates.Fil: Saporiti, F.. Universidad de Buenos Aires. Facultad de Ingeniería. Departamento de Ingeniería Mecánica. Grupo de Materiales Avanzados; Argentina;Fil: Juarez, R. E.. Universidad de Buenos Aires. Facultad de Ingeniería. Departamento de Ingeniería Mecánica. Grupo de Materiales Avanzados; Argentina;Fil: Audebert, Fernando Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Tecnologías y Ciencias de la Ingeniería; Argentina; Universidad de Buenos Aires. Facultad de Ingeniería. Departamento de Ingeniería Mecánica. Grupo de Materiales Avanzados; Argentina;Fil: Boudard, M.. Centre National de la Recherche Scientifique. Laboratoire des Matériaux et du Génie Physique; Francia

Similar frequency of Porcine circovirus 3 (PCV‐3) detection in serum samples of pigs affected by digestive or respiratory disorders and age‐matched clinically healthy pigs

Porcine circovirus 3 (PCV‐3) has been identified in pigs affected by different disease conditions, although its pathogenicity remains unclear. The objective of the present study was to assess the frequency of PCV‐3 infection in serum samples from animals suffering from post‐weaning respiratory or digestive disorders as well as in healthy animals. A total of 315 swine serum samples were analysed for PCV‐3 DNA detection by conventional PCR; positive samples were further assayed with a quantitative PCR and partially sequenced. Sera were obtained from 4 week‐ to 4 month‐old pigs clinically diagnosed with respiratory (n = 129) or digestive (n = 126) disorders. Serum samples of age‐matched healthy animals (n = 60) served as negative control. Pigs with clinical respiratory signs had a wide variety of pulmonary lesions including suppurative bronchopneumonia, interstitial pneumonia, fibrinous‐necrotizing pneumonia and/or pleuritis. Animals with enteric signs displayed histopathological findings like villus atrophy and fusion, catarrhal enteritis and/or catarrhal colitis. Overall, PCV‐3 DNA was detected in 19 out of 315 analysed samples (6.0%). Among the diseased animals, PCV‐3 was found in 6.2% (8 out of 129) and 5.6% (7 out of 126) of pigs with respiratory and digestive disorders, respectively. The frequency of PCV‐3 PCR positive samples among healthy pigs was 6.7% (4 out of 60). No apparent association was observed between PCR positive cases and any type of histopathological lesion. The phylogenetic analysis of the partial genome sequences obtained showed high identity among viruses from the three groups of animals studied. In conclusion, PCV‐3 was present in the serum of diseased and healthy pigs to similar percentages, suggesting that this virus does not seem to be causally associated with respiratory or enteric disorders.info:eu-repo/semantics/acceptedVersio

Longer and less overlapping food webs in anthropogenically disturbed marine ecosystems: confirmations from the past

This is the final version of the article. Available from the publisher via the DOI in this record.The human exploitation of marine resources is characterised by the preferential removal of the largest species. Although this is expected to modify the structure of food webs, we have a relatively poor understanding of the potential consequences of such alteration. Here, we take advantage of a collection of ancient consumer tissues, using stable isotope analysis and SIBER to assess changes in the structure of coastal marine food webs in the South-western Atlantic through the second half of the Holocene as a result of the sequential exploitation of marine resources by hunter-gatherers, western sealers and modern fishermen. Samples were collected from shell middens and museums. Shells of both modern and archaeological intertidal herbivorous molluscs were used to reconstruct changes in the stable isotopic baseline, while modern and archaeological bones of the South American sea lion Otaria flavescens, South American fur seal Arctocephalus australis and Magellanic penguin Spheniscus magellanicus were used to analyse changes in the structure of the community of top predators. We found that ancient food webs were shorter, more redundant and more overlapping than current ones, both in northern-central Patagonia and southern Patagonia. These surprising results may be best explained by the huge impact of western sealing on pinnipeds during the fur trade period, rather than the impact of fishing on fish populations. As a consequence, the populations of pinnipeds at the end of the sealing period were likely well below the ecosystem's carrying capacity, which resulted in a release of intraspecific competition and a shift towards larger and higher trophic level prey. This in turn led to longer and less overlapping food webs.Fundacio´n BBVA funded this research as part of the project ‘‘Efectos de la explotacio´n humana sobre depredadores apicales y la estructura de la red tro´fica del Mar Argentino durante los u´timos 6000 an˜os’’ (BIOCON08-194/09 2009-2011). Agencia Nacional de Promocio´n Cientı´fica y Tecnolo´gica (Argentina) provided additional funding through the project ‘‘Ana´lisis del uso de los recursos tro´ficos y su relacio´n con cambios en la abundancia en tres predadores tope del Mar Argentino’’. FS has been supported by an FPU Fellowship granted by the Spanish Ministerio de Educacio´n, Cultura y Deporte (AP 2009- 4573). Half of the cost of the publication of this article has been funded by the University of Barcelona. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Frequency of Detection and Phylogenetic Analysis of Porcine circovirus 3 (PCV-3) in Healthy Primiparous and Multiparous Sows and Their Mummified Fetuses and Stillborn

Porcine circovirus 3 (PCV-3) has been suggested as a putative causal agent of swine reproductive disease. A number of different studies have pointed out this association, but there is still a lack of information regarding the normal rates of PCV-3 infection in farms with normal reproductive parameters. The objective of the present study was to assess the frequency of PCV-3 detection in primiparous and multiparous sows and in tissues from their respective fetuses from farms with average reproductive parameters. Sera from 57 primiparous and 64 multiparous sows from 3 different farms were collected at two time points. Brain and lung tissues from 49 mummies and 206 stillborn were collected at farrowing. Samples were tested by PCR, and when positive, quantified by quantitative PCR. Thirty-nine complete genomes were obtained and phylogenetically analyzed. All sera from multiparous sows were negative, while 19/57 (33.3%) primiparous sows were PCV-3 PCR positive. From the 255 tested fetuses, 86 (33.7%) had at least one tissue positive to PCV-3. The frequency of detection in fetuses from primiparous sows (73/91, 80.2%) was significantly higher than those from multiparous ones (13/164, 7.9%). It can be concluded that PCV-3 is able to cause intrauterine infections in absence of overt reproductive disorders.info:eu-repo/semantics/publishedVersio

An in silico structural approach to critical quality attributes assessment of biopharmaceutical products

\u201cQuality by design\u201d (QbD) is a key approach in modern pharmaceutical development, applied during the development, the manufacturing and the whole life cycle of the product, included the post approval phase, for assuring the quality in terms of efficacy and safety. In detail, QbD process includes the critical quality attributes (CQAs) assessment, providing a comprehensive understanding of the product itself and the manufacturing process. CQAs are defined as \u201call the physical, chemical, biological, or microbiological properties or characteristics that should be within an appropriate limit, range, or distribution to ensure the desired product quality\u201d (ICH Q8). They have a potential impact on bioactivity, PK, immunogenicity and safety and are associated with the drug substance and drug product. In the context of biotechnological products, the introduction of a structural investigation in an early identification of potential CQAs (pCQAs) can be very useful to QbD approach. Identification of pCQAs of biomolecules can lead the characterization process during the development phase in order to ensure the desired drug quality profile. Monoclonal antibodies (mAbs), fusion proteins and antibody-drug conjugates (ADC) represent one of the most innovative class of biopharmaceuticals, due to their ability to specifically recognize unique epitopes inducing specific therapeutic responses. CQAs assessment for these biopharmaceuticals is a complex analysis due to the lack of structural information. Actually, there is only one fully-crystallized human IgG1 (PDB entry: 1HZH) and, in absence of whole structures, it is challenging to understand the impact of structural insights on the therapeutic response. On these basis, the purpose of this study was to develop an in silico strategy to build the atomistic model of the whole structure of an IgG1, focusing on lambda and kappa light chains. To reach this goal, we used a structural chimeric approach that, using the Homology Modeling (HM) tool by MOE software, allowed us to build the full atomistic model of two therapeutic and commercially available IgG1: adalimumab (kappa chain) and avelumab (lambda chain). This allowed us to investigate structural differences between two isotypes, kappa and lambda, and understand the impact of these different characteristics on the antibody structure and function. Our results try to fill the gap between biological and structural properties on biotechnological products, created by lack of full immunoglobulin crystal structures. Moreover, this innovative structural approach can be used in CQAs assessment during the pharmaceutical development and production phases, giving an important resource to pharmaceutical companies. DISCLOSURES Merck Serono, Guidonia Montecelio-Rome, Italy is an affiliate of Merck KGaA, Darmstadt, Germany. Please note that avelumab has been approved in various countries for the treatment of metastatic Merkel cell carcinoma and in the US for treatment of advanced urothelial carcinoma progressed after platinum-containing treatment

Effect of Alloying Elements in Melt Spun Mg-alloys for Hydrogen Storage

In this paper we report the effect of alloying elements on hydrogen storage properties of melt-spun Mg-based alloys. The base alloys Mg90Si10, Mg90Cu10, Mg65Cu35 (at%) were studied. We also investigated the effect of rare earths (using MM: mischmetal) and Al in Mg65Cu25Al10, Mg65Cu25MM10 and Mg65Cu10Al15MM10 alloys. All the melt-spun alloys without MM show a crystalline structure, and the Mg65Cu25MM10 and Mg65Cu10Al15MM10 alloys showed an amorphous and partially amorphous structure respectively. At 350˚C all the alloys had a crystalline structure during the hydrogen absorption-desorption tests. It was observed that Si and Cu in the binaries alloys hindered completely the activation of the hydrogen absorption. The partial substitution of Cu by MM or Al allowed activation. The combined substitution of Cu by MM and Al showed the best results with the fastest absorption and desorption kinetics, which suggests that this combination can be used for new Mg-alloys to improve hydrogen storage properties

Donor Lymphocyte Infusions After Allogeneic Stem Cell Transplantation in Acute Leukemia: A Survey From the Gruppo Italiano Trapianto Midollo Osseo (GITMO)

We conducted a retrospective multicenter study including pediatric and adult patients with acute leukemia (AL) who received donor lymphocyte infusions (DLIs) after allogeneic hematopoietic stem cell transplantation (HCT) between January 1, 2010 and December 31, 2015, in order to determine the efficacy and toxicity of the immune treatment. Two hundred fifty-two patients, median age 45.1 years (1.6\u201373.4), were enrolled from 34 Italian transplant centers. The underlying disease was acute myeloid leukemia in 180 cases (71%). Donors were HLA identical or 1 locus mismatched sibling (40%), unrelated (40%), or haploidentical (20%). The first DLI was administered at a median time of 258 days (55\u20133,784) after HCT. The main indication for DLI was leukemia relapse (73%), followed by mixed chimerism (17%), and pre-emptive/prophylactic use (10%). Ninety-six patients (38%) received one single infusion, whereas 65 (26%), 42 (17%), and 49 patients (19%) received 2, 3, or 654 infusions, respectively, with a median of 31 days between two subsequent DLIs. Forty percent of evaluable patients received no treatment before the first DLI, whereas radiotherapy, conventional chemotherapy or targeted treatments were administered in 3, 39, and 18%, respectively. In informative patients, a few severe adverse events were reported: grade III\u2013IV graft versus host disease (GVHD) (3%), grade III\u2013IV hematological toxicity (11%), and DLI-related mortality (9%). Forty-six patients (18%) received a second HCT after a median of 232 days (32\u20131,390) from the first DLI. With a median follow-up of 461 days (2\u20133,255) after the first DLI, 1-, 3-, and 5- year overall survival (OS) of the whole group from start of DLI treatment was 55, 39, and 33%, respectively. In multivariate analysis, older recipient age, and transplants from haploidentical donors significantly reduced OS, whereas DLI for mixed chimerism or as pre-emptive/prophylactic treatment compared to DLI for AL relapse and a schedule including more than one DLI significantly prolonged OS. This GITMO survey confirms that DLI administration in absence of overt hematological relapse and multiple infusions are associated with a favorable outcome in AL patients. DLI from haploidentical donors had a poor outcome and may represent an area of further investigation

The Impact of Graft CD3 Cell/Regulatory T Cell Ratio on Acute Graft-versus-Host Disease and Post-Transplantation Outcome: A Prospective Multicenter Study of Patients with Acute Leukemia Undergoing Allogeneic Peripheral Blood Stem Cell Transplantation

Although it is well known that tumor site- or bone marrow-infiltrating regulatory T cells (Tregs) might be correlated with worse outcomes in solid tumors and acute leukemias by promoting immune surveillance escape, their contribution to the immediate post-allogeneic transplantation phase by peripheral blood (PB) allografts remains unclear. Moreover, the Treg content in stem cells harvested from PB has been suggested to be correlated with acute graft versus-host-disease (aGVHD) and immunologic recovery after allogeneic PB stem cell transplantation (allo-PBSCT). This study aimed to investigate the impact of the graft content of Tregs, as graft CD3+/Tregs ratio (gCD3/TregsR), on acute GVHD and post-allo-PBSCT outcomes. We prospectively enrolled 94 consecutive patients at 9 Italian centers of the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) with acute myelogenous (n = 71; 75%) or lymphoblastic (n = 23; 25%) leukemia in complete remission who underwent matched related donor (n = 35; 37%) or unrelated donor (n = 59; 63%) allo-PBSCT. The median graft CD3+ cell, Treg, and gCD3/TregsR values were 196 × 106/kg body weight (range, 17 to 666 × 106/kg), 3 × 106/kg (range, 0.1 to 35 × 106/kg), and 71 (range, 1 to 1883), respectively. The discriminatory power of the gCD3/TregsR value to predict grade ≥II aGVHD was assessed by estimating the area under the receiver operating characteristic (ROC) curve (AUC). Any grade and grade ≥II aGVHD occurred in 24 (26%) and 17 (18%) allo-PBSCT recipients, respectively. By ROC analysis, AUC (0.74; 95% confidence interval [CI], 0.608 to 0.866; P =.002) identified 70 as the optimal gCD3/TregsR cutoff value predicting the appearance of grade ≥II aGVHD with 76% sensitivity and 71% specificity. Patients were subdivided into a high (ROC curve value ≥70) gCD3/TregsR group (HR; n = 48) and a low (ROC curve value <70) gCD3/TregsR group (LR; n = 46). The incidence of grade II-IV aGVHD was lower in the LR group compared with the HR group (9% [4 of 46] versus 27% [13 of 48]) in both univariate analysis (odds ratio [OR], 4.8; 95% CI, 1.44 to 16.17; P =.015) and multivariate analysis (OR, 5.0; 95% CI, 1.34 to 18.93; P =.017), whereas no differences were documented taking into account aGVHD of any grade. The overall survival, disease-free survival, nonrelapse mortality, and relapse rates at 2 and 3 years were 61% and 54%, 62% and 55%, 15% and 23%, and 27% and 30%, respectively. Of note, gCD3/TregsR did not significantly correlate with relapse (P =.135). Taken together, our data from this prospective multicenter study confirm the value of Tregs in preventing aGVHD while maintaining the graft-versus-leukemia effect. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc

Severe fludarabine neurotoxicity after reduced intensity conditioning regimen to allogeneic hematopoietic stem cell transplantation: a case report

We present a case of severe, irreversible neurotoxicity in a 55-year-old-patient with myelofibrosis undergoing hematopoietic stem cell transplantation following a reduced intensity conditioning including fludarabine. The patient developed progressive sensory-motor, visual and consciousness disturbances, eventually leading to death. MRI imaging pattern was unique and attributable to fludarabine neurotoxicit